Group A Streptococci (GAS) diseases remain a major public health problem in developing countries, reaching 600 million registered cases with 233,000 deaths per year. Rheumatic fever (RF) is considered an autoimmune disease resulting from the defense immune response triggered against the group A beta hemolytic streptococcus, or S. pyogenes. In some individuals (those with susceptibility to the illness), it produces an aggressive response against the organism's own proteins through biological mimicry mechanisms. If not treated properly they can lead to autoimmune post-streptococcal sequels such as RF that affects mainly children and teenagers. Rheumatic heart disease (RHD) is the most serious sequel of RF, leading to progressive and permanent heart valvular lesions.
The M-protein sequences of streptococcus were analyzed and published in the 1980s (Manjulae Philipis, 1984, and Miller et al, 1998), and permitted great advances in the knowledge of the regions capable of triggering the illness.
The M-protein contains regions of repetitions of amino acid residues, and is subdivided into an amino-terminal portion and a carboxy-terminal portion. In the amino-terminal portion are the residues of amino acids that define the streptococcus serotype. The carboxy-terminal portion (C-portion) is quite conserved among the different serotypes and has groups of amino acids that repeat themselves more than once (Fischetti, 1991).
Several segments of the amino-terminal region are involved in the triggering of RF and/or chronic RHD, especially through cross-reaction with proteins of the cardiac tissue (Cunningham, 2000 and Guilherme et al, 2005).
Several events lead to RF and RHD that leads to permanent heart-tissue lesions. Several genes are involved in the development of both RF and RHD. The inflammatory process that results from S. pyogenes infection involves the activation of several molecules such as VCAM and ICAM, which play a role in the migration of leukocytes to the heart, particularly to the valves. Specific chemokines, such as CXCL3/MIP1α as well as CCL1/I309 and CXCL9/Mig, attract T cells to the myocardium and valves, respectively and are responsible for intense inflammatory reactions that will result in the autoimmune heart-tissue lesions in RHD patients. These reactions are mediated by both the B- and T-cell responses that begin at the periphery, followed by the migration and infiltration of T-cell clones to the heart. These cells recognize streptococcal antigens and human tissue proteins. Molecular mimicry between streptococcal M protein and human proteins has been proposed as the triggering factor leading to autoimmunity in RF and RFID (Cunningham 2000 and Guilherme 2011). The production of cytokines from peripheral and heart-infiltrating mononuclear cells suggests that T helper 1 (Th1) and Th17 cytokines are the mediators of RHD heart lesions. The low numbers of IL-4-producing cells in the valvular tissue and also the low numbers of T regulatory cells in the peripheral blood might contribute to the maintenance and progression of the valve lesions. The identification of the StreptInCor epitope (Guilherme, et al., 2011) that presents the capacity of inducing T cells that regulate the inflammatory process in the heart opens a perspective of a new treatment for RF and RHD.